The SCIENCE behind the latest recommendations on ... 4/Sabah Room/Day 4_1200-1300_revi… · The...
Transcript of The SCIENCE behind the latest recommendations on ... 4/Sabah Room/Day 4_1200-1300_revi… · The...
The SCIENCE behind the latest
recommendations on prebiotics
in allergy
20 October 2016 KUALA LUMPUR
Johan Garssen, PhD, MDProfessor “Immunopharmacology”
• CVDs
• Diabetes/Obesity
• Cancer
• COPD/ASTHMA
• Autoimmunity
• IBD
• Brain/Behaviour disorders
(autism/parkinsons/alzheimers/depression…)
• Allergies
• HIV (therapy related NCD)
• Ageing/Immunosenescence
• …
• Altered environmental diversity (dysbiosis)?
• Altered lifestyle?
• Industrial technologies?
• Altered antigen/allergen exposure?
• Pollution?
• Dietary changes?
• Microbial exposure hypothesis?
• Change in infectious triggers?
• ???
No change in genes!!
Key role for immune system!!
Why are NCDs so increasingly common?
Defence against pathogens: bacteria, viruses, parasites, fungi
Assistance in anti-cancer responses
Removal of foreign / non-self compounds
Inhibition self-reactive / auto-reactive responsiveness
[Impairment of “auto-immunity” (SLE, MS, RA,…)]
Inhibition “over-activity/allergy” (mucosal and systemic tolerance)
Regulation metabolism (immuno-metabolism)
Tissue repair
Barrier regulation (gut, respiratory tract, brain, placenta, liver, thymus,
kidney)
Major tasks Immune System
Granulocyte
Macrophage / Monocyte
Dendritic cell
T Lymphocyte
(Th1, Th2, Th3, Tr, ...)
B Lymphocyte / Antibodies
Natural Killer Cell
Epithelial cell
Bone marrow
Lymph nodes
Spleen
Thymus
Organs Cells
Neurons, nerves
60-70% of “immune cells” localized in the
gastro-intestinal tract
Immune System
The GUT:
A Complex Neuro-Endocrine-Immune Organ
60 -70% of immune cells
Surface of approximately
300m2
100 million neurons
100 trillion bacteria
“ Gut Microbiota”
Dietary intervention as a tool for ‘immune’ regulation
(inflammation management)?
Utrecht University
Kraneveld, Nijkamp and Garssen 2009, EJP
Rietdijk, van Wezel, Garssen and Kraneveld 2016, Neuroimmunology Neuroinflammation
Immune regulation in the gut
CROSS TALK
years0 1 2 5 10 40 50 60 70 80 90
Th 1
Th 2
Th1 and Th2 activity as function of age
Belinda Van’t Land, Günther Boehm, Johan Garssen:
Breast milk: components with immune modulating potential and their possible role in immune mediated disease resistance.
In Dietary Components and Immune Function, Series: Nutrition and Health. Editors, Watson, Ronald R.; Zibadi, Sherma; Preedy, Victor R. 2011
• Genes
• Hygiene
• Antibiotics
• C-section
• Microbiota
• Drugs
• Diets
• Stress
• Hormones
• Infections
• Cancer
• …
Allergy
ARTHRITIS
INFECTIONS
ALLERGIES
DIABETES, OBESITY
NEC
IMMUNOSENESENCE
CANCERCACHEXIA
COPD
AUTISM
ALZHEIMERPARKINSON
Significant increase in
immune related disorders:
•Allergies, Asthma
•Autoimmunities
•IBD
•ADHD/AUTISM
•Obesity
•Diabetes
•Metab. syndrome
•…
•…
Inverse relationship between the incidence of infectious disease (top) and immune disease
(bottom) from 1950 to 2000. (Jean-Francois Bach/NEJM)
Programmed early in life?!
Th1 , Th2 , Th1/Th2
Th1
Th2 (type I allergy)
Th2
Th2
Th1
Th1 ?
Th1
Th1
Th1 , Th2
HIV
COPD
Allergies
Asthma
Atopic eczema
Coeliac disease
Cystic Fibroses
Cancer
Elderly
Infants
i
n
f
l
a
m
m
a
t
i
o
n
Autoimmunities Th1 , Th2
Immune dysregulation and NCDs
Role in metabolic disorders/diabetes/syndrome X/ obesity: immunometabolism
Role in cachexia/sarcopenia
Role in neurological disorders: Autism, Alzheimer, Depression, Hyperactivity Syndrome, ...
Utrecht University
Hyper immune- responsiveness:
Allergy
Autoimmunity
Chronic inflammatory diseases
Hypo immune- responsiveness:
Infections
Tumors/metastasis
Immune disorders and NCDs
Global Health-WUN
(2014, 2015, 2016, 2017) Cape Town, Frankfurt, Maastricht, New York
Inflammation
(management)
• Altered environmental diversity (dysbiosis)?
• Altered lifestyle?
• Industrial technologies?
• Altered antigen/allergen exposure?
• Pollution?
• Dietary changes?
• Microbial exposure hypothesis?
• Change in infectious triggers?
• ???
Why are NCDs so increasingly common?
Increased pro-inflammatory diet?
Decreased microbial
diversity?Inhaled pollutants?
S. Prescott, Perth, Australia
PREVENTION OF NCDs
Early life: Setting the Right Course for Later Life
CONCEPTION TODDLERHOOD ADULTHOOD
-9m to 24mCritical window of
opportunity to support
healthy later life
Altered growthand development
Stunting
Allergy
Obesity
Coronary heart
disease
Diabetes
Cognitive decline
HEALTHY
DISEASE
Immune Programming
years0 1 2 5 10 40 50 60 70 80 90
Th 1
Th 2
Th1 and Th2 activity as function of age
Belinda Van’t Land, Günther Boehm, Johan Garssen:
Breast milk: components with immune modulating potential and their possible role in immune mediated disease resistance.
In Dietary Components and Immune Function, Series: Nutrition and Health. Editors, Watson, Ronald R.; Zibadi, Sherma; Preedy, Victor R. 2011
• Genes
• Hygiene
• Microbiota
• Drugs
• Diets
• Stress
• Hormones
• Infections
• Cancer
• …
Allergy
Immune fitness/balance
Ability to Adapt
Activation
Pro-inflammation
(Oral) Tolerance
Anti-inflammation
Pathogenic bacteria
Virusses
Parasites
Commensal bacteria (microbiota)
Food antigens
Environmental antigens
TregsTh1/Th2
Th17
R. Kelishadi, S. Farajian. Adv Biomed Res. 2014; 3 The protective effects of breastfeeding on chronic non-communicable diseases in
adulthood: A review of evidence
Energy
Growth
Immunity
Signaling
Proteins
HMOS
An Orchestra of Complex Functions in a Complex Matrix
COMPOSITION & BENEFITS OF HUMAN MILK
Fat / LCPUFA
Lactose
Microbiota
Immunity
Digestion
Nucleotides
Minerals
Vitamins
Bacteria
+ 88% Water
Energy
Immunity
Brain
GrowthImmunityBrain
Microbiota
Immunity
Digestion
Hydration
Immunity…
GrowthImmunity
GrowthBone & TeethBlood
Hormons
GrowthMood
Living Cells
1. Microbiome management (Pro-, Pre-, Syn-, Post-
biotics)
2. Epitopes
3. Antigens/Allergens
4. lcPUFAs
5. Exosomes/lipid vesicles
6. Amino-acids
7. Enzymes
8. Peptides
9. …
New nutritional concepts for immune
development/inflammation management
early in life
IMPACT FOR ALLERGIES
1886
2016
1900s
1920s
1950s
T Escherich
Microbiota
in BF infants
E Moro
H Tissier
Bifidus
in BF infants
P György
HMOS as
Bifidus factor
1960s
1980s
1990s
1970s
Kunz HPAEC
Thurl HPAEC
Stahl MALDI for OS
Stahl sc/lc HMOS
Thurl 4 groups
2000s
Morrow Anti-infection
Kunz Immunmodulation
Newburg Antiifection
Martin Bifidus and Lb in HM
Sela Bifidus enzymes…..
CHO in milks differ
Eschbach
Deniges
HMOS
building blocks
Schönfeld
Polonowski
Lespagnol
First separation
of HMOS
Kuhn
3 groups
of HMOS
Kobata
Characterisation
of sc HMOS
Montreuil
Kobata
Egge FAB MS
Adapted from:
Bode L, Review, Glycobiology vol. 22 no. 9 pp. 1147–1162, 2012
Kunz C Adv Nutr. 2012 May; 3(3): 430S–439S
Kobata A Proc Jpn Acad Ser B Phys Biol Sci. 2010 July 21; 86(7): 731–747
PRE-PRO-BIOTICS & PEDIATRICS ≈ 130 Y
Nutr
icia
Re
se
arc
h©
A PRE-biotic is non-digestible food ingredient that, when consumed in sufficient amounts, selectively stimulates the growth and/or activity of one or a limited number of microbes in the colon resulting in documented health benefits
Examples:
Galacto-Oligosaccharides
Fructo-Oligosaccharides
Inulin
HMOS
...
DRY MATTER OF HUMAN MILK
30-50 g/l
8-10 g/l
PrebioticHMOS
adapted from:
Newburg DS, Neubauer SH: In: RG Jensen (ed):
Human milk composition Academic Press 1995; 273-349
10-12 g/l
HMOS: ESTIMATED > 1000 STRUCTURES
Mass Spec of HMOS
Stahl B, Thurl S, et al. Analyt. Biochem. 1994; 223:218-226
Th1 , Th2 , Th1/Th2
Th1
Th2 (type I allergy)
Th2
Th2
Th1
Th1 ?
Th1
Th1
Th1 , Th2
HIV
COPD
Allergies
Asthma
Atopic eczema
Coeliac disease
Cystic Fibroses
Cancer
Elderly
Infants
i
n
f
l
a
m
m
a
t
i
o
n
Autoimmunities Th1 , Th2
Immune dysregulation and NCDs
HMOS reduces diabetes incidence in later life
Diabetes development Urine glucose score results
Food intake & body weight were similar
between experimental groups
0 2 4 6 8 1 0 1 2 1 4 1 6 1 8 2 0 2 2 2 4 2 6 2 8 3 0
0
2 0
4 0
6 0
8 0
1 0 0
W e e k s o f fo llo w -u p
Dia
be
tes
-fre
e s
urv
iva
l (%
)
C o n tro l (n = 1 9 )
H M O S (n = 2 0 )
p = 0 .0 2 6
D ia te r y
in te r v e n t io n
C o n tr o l H M O S
0
1
2
3
4
5
Me
an
no
rm
ali
ze
d
ins
uli
tis
so
co
re
p < 0 .0 0 1
Normalized score (range 0-4)
C o n tr o l H M O S
0
5
1 0
1 5
2 0
% C
D2
5 o
f C
D4
ce
lls
p = 0 .0 1
Reduced Overall Immune Hyperactivation
Induction of Immune fitness
c o n tr o l H M O S
0
5
1 0
1 5
2 0
p = 0 .0 3
% C
D6
9 o
f C
D4
ce
lls
C o n tr o l H M O S
0
1 0
2 0
3 0
4 0
Se
ru
m I
L-1
7 (
pg
/mL
)
p = 0 .0 2
Second point End point
Dietary intervention
start
First point
4 weeks after
dietary intervention
20 weeks after
dietary intervention
Time points of fecal sample collection
0 2 4 6 8 1 0 1 2 1 4 1 6 1 8 2 0 2 2 2 4 2 6 2 8 3 0
0
2 0
4 0
6 0
8 0
1 0 0
W e e k s o f fo llo w -u p
Dia
be
te
s-fre
e s
urv
iva
l (%
)
C o n tro l (n = 1 9 )
H M O S (n = 2 0 )
p = 0 .0 2 6
D ia te r y
in te r v e n t io n
F ir s t p o in t S e c o n d p o in t E n d p o in t
Changes of phylum distribution of fecal samples over time
Second point
End point
Control diet HMOS diet
First point
Mora Murri et al., 2013
Ratio of Firmicutes/Bacteroidetes in diabetic and healthy
individuals
The Ratio of Firmicutes/Bacteroidetes declined over time in the individuals
who developed T1D, while the inverse pattern was observed in the healthy
individuals.
Negative correlation between this ratio and the glucose levels in children
with T1D.
Ling X, Astrid H, et. al. Submitted 2016
Hypothetical interplay between gut microbiota and intestinal
immune system by HMOS
Bacterial components
(i.e. LPS)
HMOS activate Tregs with anti-inflammatory properties.
HMOS decrease antigen exposure to the mucosal system .
HMOS beneficilally induce toleragenic DCs differentiation.
HMOS increase mucin synthesis therefore maintain gut intergrity and inhibit pathogen adhension.
Conclusions Early HMOS diet suppresses
autoimmune diabetes development in
NOD mice later in life.
Associated with milder insulitis, lower
induction of Th1 cells, overall immune
activation markers expression and down-
regulation of serum IL-17.
Maybe related to regulation of intestinal
microbiota.
HMOS in early life modulate T1D in
later life: an example of immunological
programming.
WIRM award
2016 DAVOS
Vos AP, Haarman M, Buco A, Govers M, Knol J, Garssen J, Stahl B, Boehm G, M'rabet L. Int Immunopharmacol. 2006;6(8):1277-86
2% 2% 2% 2%
0
20
40
60
80
100
120
140
160
Cell
ula
r im
mu
nit
y (
DT
H)
Flu
va
cc
ina
tio
n r
es
po
nse
(1
0-3
mm
)
*
NOT ALL PREBIOTICS ARE THE SAME
0.8
g/100ml
(n=27)
0
g/100ml
(n=33)
0.4
g/100ml
(n=30)
log 1
0 o
f C
FU
/g w
et
faeces (
media
n, IQ
R)
2
3
4
5
6
7
8
9
10
11
12
Reference range (IQR) of breastfed infants (n=15)
Group difference according to Mann-Whitney U-test: * p<0.05 vs. 0.0, # vs. 0.4
**#
Unique oligosaccharides PROMOTE HEALTHY
BACTERIA & pH
Moro G, Minoli I, Mosca M, Jelinek J, Stahl B, Boehm G. J Pediatr Gastroenterol Nutr 2002; 34:291-295
-1.5
-1.0
-0.5
0
+0.5
+1.0
+1.5
Ch
ange
in s
too
l pH
day
28
vs.
day
0(m
ean
s
SD)
*
*#
0.8g/100ml
(n=27)
0g/100ml(n=33)
0.4g/100ml(n=30)
reference range (IQR) ofbreastfed infants (n=15)
* p<0.01 vs. 0.0, # vs. 0.4 according to ANOVA and Fisher post-hoc-test
Bifidus Change in stool pH
• Safe, Food-Grade Source
• Approved as Food or Food Ingredient
• Exact Characterization
• Chemical and Physical Properties
(No Negative Effect Like: Complexing of Minerals, Vitamins and Fats)
• Physiologic Parameters Like: Digestibility, Taste &Texture
• Clinical Evidence for Prebiotic Effect
CRITERIA FOR THE SELECTION OF PREBIOTICS
After: Boehm G, Fanaro S, Jelinek J, Stahl B, Marini A Acta Paediatr Suppl. 2003 Sep;91(441): 64-7.
Prebiotic concept for infant nutrition..
EFFECTS ON STOOL CHARACTERISTICS
Scholtens, PAMJ, Goossens DAM, Staiano A
World J Gastroenterol. 2014 Oct 7; 20(37):
13446–13452.
http://www.ilsi.org/Europe/Pages/TF_Prebiotics.aspx
FREE ACCESS
Review on Prebiotics by
ILSI-Europe Task Force
Prebiotic Effect: Established Scientific Fact
GRAS Notice (GRN) No.477
http://www.fda.gov/Food/IngredientsPackagingLabeling/
GRAS/NoticeInventory/default.htm
COMMISSION DIRECTIVE 2006/141/EC 2006 on infant formulae and
follow-on formulae and amending Directive 1999/21/EC
…the WAO guideline panel suggests using prebiotic
supplementation in not-exclusively breastfed
infants ….
SYSTEMATIC REVIEW 2016:
PREBIOTICS ON ALLERGY PREVENTION
Potential Mechanisms for Immune
Fitness by unique oligosaccharides
Vos AP, M’rabet L, Stahl B, Boehm G, Garssen J.
Critical Reviews. Immunology 2007
Prebiotic
Effects
Direct
Effects
Th1 , Th2 , Th1/Th2
Th1
Th2 (type I allergy)
Th2
Th2
Th1
Th1 ?
Th1
Th1
Th1 , Th2
HIV
COPD
Allergies
Asthma
Atopic eczema
Coeliac disease
Cystic Fibroses
Cancer
Elderly
Infants
i
n
f
l
a
m
m
a
t
i
o
n
Autoimmunities Th1 , Th2
Immune dysregulation and NCDs
A model for NCDs?
0
0,05
0,1
0,15
0,2
0,25
0,3
0,35
0,4
0,45
HIV asymptomatic persons Healthy persons
% o
f to
tal b
ac
teri
al lo
ad
(g
eo
me
tric
me
an
)
HIV asymptomatic Healthy
Lac
tob
ac
illi (
%)
0
0,5
1
1,5
2
2,5
3
3,5
4
4,5
5
HIV asymptomatic persons Healthy persons
% o
f to
tal b
ac
teri
al lo
ad
(g
eo
me
tric
me
an
)
HIV asymptomatic Healthy
Bif
ido
bac
teri
a (
%)
HIV asymptomatic Healthy Healthy
Ca
nd
ida
alb
ican
s
(ce
lls
/g w
et
we
igh
t fe
ac
es
)
1.00E+03
1.00E+04
1.00E+05
1.00E+06
1.00E+07
HIV asymptomatic
Ps
eu
do
mo
na
s (
%)
Gori A et al. J Clin Med (2008); Mucosal Immunology (2011)
Altered gut microbiota in HIV infected individuals
COPA trial ,Gori A et al (2011) Mucosal immunology
Expressed as median (range)
15g/d 30g/d
Expressed as mean ± se
15g/d 30g/d
Prebiotic Oligo’s improve the Gut Microbiota of HIV infected Adults
Changes from baseline in activated CD4+ T cells (% CD4+CD25+) during the 52-week
intervention period in the intention-to-treat population from a BITE pilot study (*P = .036,
change from baseline).
Cahn P et al. Clin Infect Dis. 2014;57:139-146
Th1 , Th2 , Th1/Th2
Th1
Th2 (type I allergy)
Th2
Th2
Th1
Th1 ?
Th1
Th1
Th1 , Th2
HIV
COPD
Allergies
Asthma
Atopic eczema
Coeliac disease
Cystic Fibroses
Cancer
Elderly
Infants
i
n
f
l
a
m
m
a
t
i
o
n
Autoimmunities Th1 , Th2
Immune dysregulation and NCDs
Arslanoglu S, Moro GE, Boehm G. J. Nutr.
2007 137(11): 2420-4
Protection Against Allergy-prevention
Atopic Dermatitis (infants at risk)
After 6 months
scGOS/lcFOS
(n=102)
Control
(n=104)
Cu
mu
l. i
nc
ide
nc
e o
f a
top
ic d
erm
ati
tis
10
15
25
30
0
5
20
9.8%
*
9.8%
23.1%
P=0.014 (Fisher test)
scGOS/lcFOS
(n=66)
Control
(n=68)
0
5
10
15
20
25
30
35
27.9%
13.6%
P<0.05(Fisher test)
*
Cu
mu
l. i
nc
ide
nc
e o
f a
top
ic d
erm
ati
tis
After 24 months
Arslanoglu S, Moro GE, Schmitt J, Boehm G.,
J. Nutr. 2008; 138: 1091–1095.
Significant decrease in biomarkers for allergy (serum IgE,
IgG1 and CMA IgG1 in High-Risk Infants at 6 Months)
**p=0.008
Tota l IgE
Placebo Gos/lcFos
1
10
100
1000
IgE
(kU
/l)
Hoffen et al., 2009 Allergy
P<0.0105
Placebo GOS/lcFOS
0.1
1
10
100
1000
IgG
1 (
AU
/ml)
P<0.0105
Total IgG1
(first preliminary indications for tolerance induction-IgG4/Treg)
IgE
IgG
Plasma cells Mast cell
Allergic response
Allergen challenge:
cross-linking surface-
bound Ig
Anti-histamines
Leukotriene
antagonists
NSAID’s
Corticosteroids
Anti-cytokines
Fcε
RI
FcγRI/I
II
Redegeld et al., Curr. Opin. Invest. Drugs, 2009
Redegeld et al., Nature Med 2002
Schouten et al. JACI 2010
IgLC
Inflammation response
atopic dermatitis: higher
levels of Ig-FLC in serum
Schouten et al. JACI 2010, PAI 2011
oligosaccharides down-
regulates Ig-FLC in infants at
risk for allergy
Early dietary intervention with a mixture of prebiotic
oligosaccharides reduce the incidence of allergic
manifestations during the first 2 years of life
Arslanoglu et al., 2008, J. of Nutr. 138:1091-1095
Pre
se
nc
e o
f a
ny a
lle
rgy-r
ela
ted
sym
pto
m
scGOS/lcFOS (n=40) Control (n=49)0
5
10
15
20
25
30
Cu
mu
lati
ve
in
cid
en
ce
of
all
erg
yAtopic Dermatitis Recurrent Wheezing Allergic Rhinitis
0
5
10
15
20scGOS/lcFOS
Control
Protection Against Allergy
5 year follow-up
Arslanoglu S, et al 2011
10
%
26.5
%
3.3%
12.3
%
6.7%
12.2
%
3.3%
16.3
%P < 0.05
P < 0.05 P < 0.05
Oligosaccharides reduce incidence of
Atopic Dermatitis in infants not at risk
(prevention)
Gruber et al. JACI 2010
p<0.0469
8 16 24 520
2
4
6
8
10Placebo
scGOS/lcFOS/AOS
Breastfed
Age (weeks)
Cu
mu
lati
ve i
ncid
en
ce
of
ato
pic
derm
ati
tis
The PATCH study-prevention
Study formula was provided from the moment the mother decided to stop or
supplement breastfeeding. Part of the original study population (38%) was
followed up until 3-5 years of age.
PATCH (12 – 18 months) PATCH FU (3-5 years)
Boyle, Tang et al. Allergy 2016
18 month eczema development 5 year allergic manifestations in
subgroup not weaned <18 weeks
Manuscript in preparationBoyle, Tang et al. Allergy 2016
Beneficial effect of HP + prebiotics related to the timing of
introduction of weaning foods and long-term allergy
development.
Indication of immune-modulatory capacities
of HP + prebiotics
long-term reduction of
sensitization marker
Boyle, Tang et al. Allergy 2016, manuscript in preparation
A PRO-biotic is a live microorganism
which when administered in adequate
amounts confer a health benefit on the
host (WHO/FAO 2002)
Examples:
Lactobacillus
Bifidobacterium
...
0
100
200
300
400
500
Sham-sens PBS B.animalis B. breve B. infantis L. rhamnosus L. plantarum
Tota
l num
be
r of
cells
in B
ALF
(x 1
04) Lymphocytes
MacrophagesNeutrophils
Eosinophils
B.animalis
Hougee et al. Int. Arch. Allergy Immunol., 2010; Hoffen van et al. Int Arch Allergy Immunol., 2010
.
Probiotics: strain selection is essential!!
(new concepts for allergic inflammation)
* *
?
A synbiotics is the combination of both pro- and prebiotics
Example:
Galacto-Oligosaccharides
Fructo-Oligosaccharides
B breve M16V
Fructo-Oligosaccharides
B breve M16V
Synbiotics prevent acute response for cow’s
milk allergy in vivo (preclinical studies)
Synbiotics reduce acute allergic reaction
Schouten et al. J Nutr 2009
de Kivit et al. Allergy 2012
Synbiotic effect correlated with increased galectin-9
p<0.01
p=0.033
Van de Pol et al, Allergy, 2011
Non-digestible oligosaccharides + B breve M16V reduce
Asthma Markers in Adults (treatment)
Van de Aa et al, Clin Exp All, 2010
Non-digestible oligosaccharides + B breve M16 V reduce
atopic dermatitis in children (treatment)
Synbiotics increase serum galectin-9 in infants
with atopic dermatitis (van der Aa study)
Baseline Week 12 (V4)
de Kivit et al. Allergy 2012
Noisy breathing apart from colds Frequent wheezing
p= 0.001p= 0.04
Lower Prevalence of Asthma like Symptoms in the Synbiotic group
at 1 year Follow Up
Van de Aa et al, Allergy, 2011
Less asthma medication
Non-digestible oligosaccharides + B breve M16V reduce
respiratory symptoms in children (sec. prevention)
Allergy
Obesity
Coronary Heart Disease
Diabetes
Autoimmunity
NCDs
Birth +48 months
Programming
Imprinting
Dietary intervention Prebiotics
Healthy Life
-9 months
PREVENTION of NCDs
Early life: Setting the Right Course for Later Life
Health
Disease
Role in metabolic disorders/diabetes/syndrome X/ obesity: immunometabolism
Role in cachexia/sarcopenia
Role in neurological disorders: Autism, Alzheimer, Depression, Hyperactivity Syndrome, ...
Utrecht University
Hyper immune- responsiveness:
Allergy
Autoimmunity
Chronic inflammatory diseases
Hypo immune- responsiveness:
Infections
Tumors/metastasis
Immune disorders and NCDs
Inflammation
Global Health-WUN
Dietary intervention for the management of NCDs?
Creating a healthy balance!
IMMUNE FITNESS
FIT FOR LIFE
1. Microbiome management (Pro-, Pre-, Syn-, Post-
biotics)
2. Epitopes
3. Antigens/Allergens
4. lcPUFAs
5. Exosomes/lipid vesicles
6. Amino-acids
7. Enzymes
8. Peptides
9. …
New nutritional concepts for allergy
management
1. Selective prebiotics inhibit the onset and severity of
allergy related disorders early and later in life.
PROGRAMMING.
2. Specific prebiotics induce immune biomarkers for
immune fitness and tolerance.
3. Underlying mechanisms indicate a role for gut
integrity, microbiome diversity, immune tolerance,
Tregs, and galectin 9
MAJOR CONCLUSIONS
Immune modulatory mechanisms,
allergy, inflammation, obesity,
autoimmunity, infections, NCDs, …
Grants& industry
Ongoing collaborations
CFACenter food
allergy
Ministery
VWA
UU focus grant
(neuro-mmune)
Acknowledgements/Conflicts of interest
PYRAMID OF EVIDENCE